Aminoshikimate pathway

The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer Amycolatopsis mediterranei. Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins.^[1]

Overview

Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in Amycolatopsis mediterranei.^[2] The enzyme-catalyzed condensation of 1-deoxy-1-imino-D-erythrose 4-phosphate with phosphoenolpyruvate to form 4-amino-3,4-dideoxy-d-arabino-heptulosonic acid 7-phosphate has been proposed to be the first committed step in the aminoshikimate pathway. Guo and Frost demonstrated that the unusual metabolite, 1-deoxy-1-imino-D-erythrose 4-phosphate, is derived from 3-amino-3-deoxy-D-fructose 6-phosphate.^[3] In addition, kanosamine biosynthesis has been directly implicated by Guo and Frost as the source of the aminoshikimate pathway's nitrogen atom.^[4]

Uses

Aminoshikimate pathway has been assembled in E. coli to synthesize aminoshikimic acid, which is a promising starting material for the synthesis of anti-influenza agent oseltamivir (brand name Tamiflu).^[5]^[6]

References

^ Floss, H. G. (1997). "Natural products derived from unusual variants of the shikimate pathway". Nat Prod Rep. 14 (5): 433–452. doi:10.1039/np9971400433. PMID 9364776.
^ August, P. R.; tang, L.; Yoon, Y. J.; Ning, S.; Muller, R.; Yu, T. -W.; Taylor, M.; Hoffmann, D.; Kim, C. -G.; Zhang, X.; Hutchinson, C. R.; Floss, H. G.. (1998). "Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699". Chem. Biol. 5 (2): 69–79. doi:10.1016/S1074-5521(98)90141-7. PMID 9512878.
^ Guo, Jiantao; Frost, John (2002). "Biosynthesis of 1-Deoxy-1-imino-d-erythrose 4-Phosphate: A Defining Metabolite in the Aminoshikimate Pathway". J. Am. Chem. Soc. 124 (4): 528–529. doi:10.1021/ja016963v. PMID 11804477.
^ Guo, Jiantao; Frost, John (2002). "Kanosamine Biosynthesis: A Likely Source of the Aminoshikimate Pathway's Nitrogen Atom". J. Am. Chem. Soc. 124 (36): 10642–10643. doi:10.1021/ja026628m. PMID 12207504.
^ Guo, Jiantao; Frost, John (2004). "Synthesis of Aminoshikimic Acid". Organic Letters. 6 (10): 1585–1588. doi:10.1021/ol049666e. PMID 15128242.
^ Frost, John & Jiantao Guo. US 20070190621A1 "Synthesis of oseltamivir carboxylates."

[1] Floss, H. G. (1997). "Natural products derived from unusual variants of the shikimate pathway". Nat Prod Rep. 14 (5): 433–452. doi:10.1039/np9971400433. PMID 9364776.

[2] August, P. R.; tang, L.; Yoon, Y. J.; Ning, S.; Muller, R.; Yu, T. -W.; Taylor, M.; Hoffmann, D.; Kim, C. -G.; Zhang, X.; Hutchinson, C. R.; Floss, H. G.. (1998). "Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699". Chem. Biol. 5 (2): 69–79. doi:10.1016/S1074-5521(98)90141-7. PMID 9512878.

[3] Guo, Jiantao; Frost, John (2002). "Biosynthesis of 1-Deoxy-1-imino-d-erythrose 4-Phosphate: A Defining Metabolite in the Aminoshikimate Pathway". J. Am. Chem. Soc. 124 (4): 528–529. doi:10.1021/ja016963v. PMID 11804477.

[4] Guo, Jiantao; Frost, John (2002). "Kanosamine Biosynthesis: A Likely Source of the Aminoshikimate Pathway's Nitrogen Atom". J. Am. Chem. Soc. 124 (36): 10642–10643. doi:10.1021/ja026628m. PMID 12207504.

[5] Guo, Jiantao; Frost, John (2004). "Synthesis of Aminoshikimic Acid". Organic Letters. 6 (10): 1585–1588. doi:10.1021/ol049666e. PMID 15128242.

[6] Frost, John & Jiantao Guo. US 20070190621A1 "Synthesis of oseltamivir carboxylates."

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